Mouse Fli-1 gene is shown to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have cloned and characterized the human Fli-1 gene. Our results demonstrate that Fli-1 gene codes for sequence specific DNA binding proteins that act as transcriptional activators. Fli-1 gene is also shown to be involved in several human solid tumors (Ewing family of tumors) carrying t(11;22) chromosome translocation. We have cloned the aberrant EWS-Fli-1 fusion cDNAs involved in these human solid tumors. Functional analysis of EWS-Fli-1 proteins revealed that they function as sequence specific transcriptional activators. Recent studies suggest that both oncoproteins and viral proteins play major role not only in cell proliferation but also in cell differentiation and apoptosis. Our recent results suggest that both normal and aberrant Fli-1 proteins inhibit apoptosis. We intend to study the role of DNA binding and transactivation of Fli-1 proteins in the inhibition of apoptosis. We also plan to study how Fli-i interacts with already known cell death pathways to get a clue for the role of Fli-1 and its target genes in modulating both survival and neoplastic properties of hematopoietic cells.